Potential For Secondary Exposure To Testosterone

Cases of secondary exposure resulting in virilization of
children have been reported in postmarketing surveillance. Signs and symptoms
have included enlargement of the penis or clitoris, development of pubic hair,
increased erections and libido, aggressive behavior, and advanced bone age. In
most cases, these signs and symptoms regressed with removal of the exposure to
testosterone gel. In a few cases, however, enlarged genitalia did not fully
return to age-appropriate normal size, and bone age remained modestly greater
than chronological age. The risk of transfer was increased in some of these cases
by not adhering to precautions for the appropriate use of the topical
testosterone product. Children and women should avoid contact with unwashed or
unclothed application sites in men using AndroGel 1% [see DOSAGE AND
ADMINISTRATION, Use In Specific Populations and CLINICAL
PHARMACOLOGY].

Inappropriate changes in genital size or development of
pubic hair or libido in children, or changes in body hair distribution,
significant increase in acne, or other signs of virilization in adult women
should be brought to the attention of a physician and the possibility of
secondary exposure to testosterone gel should also be brought to the attention
of a physician. Testosterone gel should be promptly discontinued until the
cause of virilization has been identified.

Polycythemia

Increases in hematocrit, reflective of increases in red
blood cell mass, may require lowering or discontinuation of testosterone. Check
hematocrit prior to initiating treatment. It would also be appropriate to
re-evaluate the hematocrit 3 to 6 months after starting treatment, and then
annually. If hematocrit becomes elevated, stop therapy until hematocrit
decreases to an acceptable concentration. An increase in red blood cell mass
may increase the risk of thromboembolic events.

Venous Thromboembolism

There have been postmarketing reports of venous
thromboembolic events, including deep vein thrombosis (DVT) and pulmonary
embolism (PE), in patients using testosterone products such as AndroGel 1%.
Evaluate patients who report symptoms of pain, edema, warmth and erythema in
the lower extremity for DVT and those who present with acute shortness of
breath for PE. If a venous thromboembolic event is suspected, discontinue
treatment with AndroGel 1% and initiate appropriate workup and management [seeADVERSE REACTIONS].

Use In Women

Due to lack of controlled evaluations in women and
potential virilizing effects, AndroGel 1% is not indicated for use in women [see
CONTRAINDICATIONS and Use In Specific Populations].

Potential For Adverse Effects On Spermatogenesis

With large doses of exogenous androgens, including
AndroGel 1%, spermatogenesis may be suppressed through feedback inhibition of
pituitary follicle-stimulating hormone (FSH) which could possibly lead to adverse
effects on semen parameters including sperm count.

Hepatic Adverse Effects

Prolonged use of high doses of orally active
17-alpha-alkyl androgens (e.g., methyltestosterone) has been associated with
serious hepatic adverse effects (peliosis hepatis, hepatic neoplasms,
cholestatic hepatitis, and jaundice). Peliosis hepatis can be a
life-threatening or fatal complication. Long-term therapy with intramuscular
testosterone enanthate has produced multiple hepatic adenomas. AndroGel 1% is
not known to cause these adverse effects.

Edema

Androgens, including AndroGel 1%, may promote retention
of sodium and water. Edema, with or without congestive heart failure, may be a
serious complication in patients with preexisting cardiac, renal, or hepatic
disease [seeADVERSE REACTIONS].

Lipids

Hypercalcemia

Androgens, including AndroGel 1%, should be used with
caution in cancer patients at risk of hypercalcemia (and associated
hypercalciuria). Regular monitoring of serum calcium concentrations is
recommended in these patients.

Decreased Thyroxine-binding Globulin

Androgens, including AndroGel 1%, may decrease
concentrations of thyroxin-binding globulins, resulting in decreased total T4
serum concentrations and increased resin uptake of T3 and T4. Free thyroid hormone
concentrations remain unchanged, however, and there is no clinical evidence of
thyroid dysfunction.

Flammability

Alcohol based products, including AndroGel 1%, are
flammable; therefore, patients should be advised to avoid fire, flame or smoking
until the AndroGel 1% has dried.

Use In Men With Known Or Suspected Prostate Or Breast
Cancer

Potential For Secondary Exposure To Testosterone And Steps
To Prevent Secondary Exposure

Secondary exposure to testosterone in children and women
can occur with the use of testosterone gel in men. Cases of secondary exposure
to testosterone have been reported in children.

Physicians should advise patients of the reported signs
and symptoms of secondary exposure which may include the following:

In children; unexpected sexual development including
inappropriate enlargement of the penis or clitoris, premature development of
pubic hair, increased erections, and aggressive behavior

In women; changes in hair distribution, increase in acne,
or other signs of testosterone effects

The possibility of secondary exposure to testosterone gel
should be brought to the attention of a healthcare provider

AndroGel 1% should be promptly discontinued until the
cause of virilization is identified

Strict adherence to the following precautions is advised
to minimize the potential for secondary exposure to testosterone from
testosterone gel in men [seeMedication Guide]:

Children and women should avoid contact with unwashed
or unclothed application site(s) of men using testosterone gel

Patients using AndroGel 1% should apply the product as
directed and strictly adhere to the following:

Wash hands with soap and water after application

Cover the application site(s) with clothing after
the gel has dried

Wash the application site(s) thoroughly with soap
and water prior to any situation where skin-to-skin contact of the application
site with another person is anticipated

In the event that unwashed or unclothed skin to which
AndroGel 1% has been applied comes in contact with the skin of another person,
the general area of contact on the other person should be washed with soap and
water as soon as possible [see DOSAGE AND ADMINISTRATION, WARNINGS
AND PRECAUTIONS and CLINICAL PHARMACOLOGY].

Potential Adverse Reactions With Androgens

Patients should be informed that treatment with androgens
may lead to adverse reactions which include:

Changes in urinary habits such as increased urination at
night, trouble starting your urine stream, passing urine many times during the
day, having an urge that you have to go to the bathroom right away, having a
urine accident, being unable to pass urine and weak urine flow.

Patients Should Be Advised Of The Following Instructions For
Use

Read the Medication Guide before starting AndroGel 1%
therapy and to reread it each time the prescription is renewed

AndroGel 1% should be applied and used appropriately
to maximize the benefits and to minimize the risk of secondary exposure in
children and women

Keep AndroGel 1% out of the reach of children

AndroGel 1% is an alcohol based product and is
flammable; therefore avoid fire, flame or smoking until the gel has dried

It is important to adhere to all recommended
monitoring

Report any changes in their state of health, such as
changes in urinary habits, breathing, sleep, and mood

AndroGel 1% is prescribed to meet the patient's specific
needs; therefore, the patient should never share AndroGel 1% with anyone.

Wait 5 hours before swimming or washing following
application of AndroGel 1%. This will ensure that the greatest amount of
AndroGel 1% is absorbed into their system.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Testosterone has been tested by subcutaneous injection
and implantation in mice and rats. In mice, the implant induced
cervical-uterine tumors which metastasized in some cases. There is suggestive
evidence that injection of testosterone into some strains of female mice
increases their susceptibility to hepatoma. Testosterone is also known to
increase the number of tumors and decrease the degree of differentiation of
chemically induced carcinomas of the liver in rats. Testosterone was negative
in the in vitro Ames and in the in vivo mouse micronucleus assays. The
administration of exogenous testosterone has been reported to suppress
spermatogenesis in the rat, dog and non-human primates, which was reversible on
cessation of the treatment.

Use In Specific Populations

Pregnancy

Pregnancy Category X

AndroGel 1% is contraindicated during pregnancy or in
women who may become pregnant. Testosterone is teratogenic and may cause fetal
harm. Exposure of a female fetus to androgens may result in varying degrees of
virilization. If this drug is used during pregnancy, or if the patient becomes
pregnant while taking this drug, the patient should be apprised of the
potential hazard to a fetus.

Nursing Mothers

Although it is not known how much testosterone transfers
into human milk, AndroGel 1% is contraindicated in nursing women because of the
potential for serious adverse reactions in nursing infants. Testosterone and other
androgens may adversely affect lactation [seeCONTRAINDICATIONS].

Pediatric Use

The safety and efficacy of AndroGel 1% in pediatric
patients less than 18 years old has not been established. Improper use may
result in acceleration of bone age and premature closure of epiphyses.

Geriatric Use

There have not been sufficient numbers of geriatric
patients involved in controlled clinical studies utilizing AndroGel 1% to
determine whether efficacy in those over 65 years of age differs from younger
subjects. Additionally, there is insufficient long-term safety data in
geriatric patients to assess the potential risks of cardiovascular disease and
prostate cancer.

Geriatric patients treated with androgens may also be at
risk for worsening of signs and symptoms of BPH.

Renal Impairment

No studies were conducted in patients with renal
impairment.

Hepatic Impairment

No studies were conducted in patients with hepatic
impairment.

Last reviewed on RxList: 7/7/2014
This monograph has been modified to include the generic and brand name in many instances.